Pyeloureteric peristalsis: role of atypical smooth muscle cells and interstitial cells of Cajal-like cells as pacemakers

Pyeloureteric peristalsis has long been considered to be triggered by pacemaker atypical smooth muscle cells (SMC) located in the proximal regions of the renal pelvis. However, interstitial cells with many of the morphological features and c-Kit immuno-reactivity of interstitial cells of Cajal (ICC), the established pacemaker cells in the intestine, have been demonstrated to be present in small numbers within the ureteropelvic junction (UPJ) of many mammals. Freshly isolated ICC-like cells (ICC-LC) of the mouse UPJ also display autorhyhmicity. This review discusses the notion that ureteric peristalsis depends on the presence of both atypical SMC and ICC-LC which form separate but interconnected networks that drive electrically quiescent typical SMC. In contrast to the intestine or prostate, all regenerative potential discharge in the mouse UPJ is abolished by the L-type Ca2+ channel blocker nifedipine revealing a fundamental pacemaker signal. Whether these pacemaker transients arise from atypical SMC or ICC-LC or both has yet to be established. We speculate that the presence of spontaneously active ICC-LC in the distal regions of the UPJ maintains rudimentary peristaltic waves and movement of urine towards the bladder after pyeloureteral obstruction or pyeloplasty and disconnection from the proximal pacemaker drive.